Drug Evaluation Committee December 2022: Handling of SAE Reports for Hospitalizations for Scheduled Surgery (Part 4)
Related Category: Adverse Event Reporting
Initial Publication Date: September 2022
Question
I would like to inquire about the Collection of Questions and Opinions for Clinical Trial No. 119, which has been made public.In the examples listed in “2008-03 Handling of SAE Reports for Hospitalization Prior to Scheduled Surgery(Part 2),” it is stated that polypectomy does not need to be judged as serious until the fact of hospitalization occurs. However, based on my own experience alone, there are a significant number of CRC investigators who interpret this broadly to mean that “as long as hospitalization is merely ‘scheduled,’ it does not need to be judged as serious under any circumstances.”
*In such cases, even if it is clear that the event would obviously affect survival or disease prognosis without surgery, it is not deemed serious if the hospitalization is “scheduled” for a later date due to factors such as operating room availability, the impact of COVID-19, or the patient’s schedule.Depending on the situation, a condition for which surgery is scheduled after the clinical trial has ended (i.e., after the follow-up period has concluded) may be deemed non-serious, leading to the trial being closed as non-serious.
Furthermore, the JPMA’s opinion in the same Q&A states, “As the clinical trial sponsor, it is necessary to gather information as quickly as possible to determine whether an event should be reported urgently (e.g., whether it resulted from a deterioration during the trial).” However, there are cases where an event is deemed not to be a SAE but is reported simply because it was requested to do so.For similar reasons, I have also encountered situations where a CRC determined that an event occurring during a clinical trial—even if it required measures or treatments typically provided during hospitalization—should not be treated as serious simply because the subject was already undergoing long-term hospitalization and the event did not result in an actual extension of that hospitalization.
Article 273 of the Pharmaceutical and Medical Devices Act states, “...hospitalization or an extension of the hospitalization period is required.” Therefore, I believe the underlying premise remains the same in any situation: events that are “required” should be judged as serious. What are your thoughts on this?
In this case, the client’s and the CRC’s opinions often conflict, which is causing us significant difficulty. It would be very helpful if you could add your opinion to the Clinical Trial 119 guidelines.Furthermore, regarding the polypectomy in 2008-03, I understand that, as per your opinion, it is possible that the event may not necessarily be judged as serious at that point from the perspective of necessity or urgency.
JPMA Opinion
“Q&A Regarding Post-Marketing Adverse Event Reports and Clinical Trial Adverse Event Reports in Accordance with the E2B (R3) Implementation Guide”(Administrative Notice dated June 24, Reiwa 4, from the Pharmaceutical Review and Management Division and the Pharmaceutical Safety Measures Division, Bureau of Pharmaceuticals and Consumer Affairs, Ministry of Health, Labor and Welfare) contains the following statement; therefore, it is considered that a serious adverse event applies not when it is determined that hospitalization or an extension of the hospitalization period is necessary, but rather when hospitalization or an extension of the hospitalization period actually occurs.Q39: [Post-Marketing] How should we interpret the phrase “cases where hospitalization at a hospital or clinic, or an extension of the hospitalization period, is deemed necessary for treatment” in Article 228-20 of the Enforcement Regulations?
A39: [Post-Marketing] This corresponds to the ICH provisions (see E2D Guideline) regarding “cases where hospitalization or extension of the hospitalization period is necessary for treatment.” This applies to cases where hospitalization or an extension of the hospitalization period is required to treat an adverse event, and also includes cases where a subject was hospitalized for treatment of an adverse event but no specific medical intervention was performed (rest and observation).(Omitted below)
On the other hand, if a new adverse event occurs in a subject who is already hospitalized, even if there is no extension of the originally scheduled hospitalization period, it is necessary to determine whether the event qualifies as a serious adverse event by considering the measures taken for that event,treatment for that event—such as whether it is the type of treatment typically performed during hospitalization or whether it meets the criteria for other serious adverse events—to determine whether it qualifies as a serious adverse event.
Since the clinical trial protocol may define the scope of serious adverse events based on the characteristics of the investigational drug or specify reporting requirements to the sponsor after the follow-up period ends, in situations such as the one described in your question, we believe it is necessary to request information from the sponsor and discuss and reach mutual agreement on how to handle such cases.